One of the greatest problems of organ transplantation lies in the short time that must elapse among the organ is available and it is transplanted in the receiver. Although it depends in many variables (the donor and type of organ), generally speaking, a kidney needs to be transplanted in 24 hours after it was available; although it may work after cold storage up to 48 hours. Heart and lungs can only be conserved around 6 hours, while liver and pancreas up to 12 hours. In any case it is always preferable to transplant as soon as possible.
However now, according to a study published in “Nature Medicine”, it may be possible to extend the organs life once they are removed from the donor thanks to an innovative supercooling system. In particular, researchers at the National Institutes of Health (NIH) in the US have successfully proved this new technique of supercooling in rats. If this is also fortunate for humans, it would remarkably increment the number of organs available to transplant, thus saving more lives.
More than 60 years ago it was held the first transplant of a solid human organ, a kidney; this was a milestone that changed modern medicine. Since then, it has been transplanted all types of organs; such as hearts, lungs, corneas, among others. Furthermore, it has also been used for tissues, such as skin. Nevertheless, due to the shortage of donor organs, waiting lists continue to grow all over the world.
With current techniques it is impossible to preserve a liver for no more than 24 hours; the methos combines low temperatures and a chemical solution developed by University of Wisconsin-Madison scientists in 1983. The solution helps keep alive the liver tissue during transit from the donor to the receiver. In this way, it has been possible to recover many organs, increasing the number of successful transplants. Although, this has not been enough; particularly in the case of the liver, which is the second organ more transplanted in Europe, after the kidney (112,631 solid organs were transplanted in the EU in 2012, from which 23,721 were livers)
The possibility of extending the preservation time of a donated liver, explained the authors, would have numerous benefits: more time to prepare the patient and facilitate the hospital donor logistic; less urgency in the collection and transfer of the organ into its destination; an increase in the donor area that could increase intercontinental and transcontinental transplants; in addition, it would beneficiate the possibility of selecting the most appropriate organ for each patient.
The biggest challenge for long-term preservation of human organs derives manly from severe tissue damage that occurs when organs are cryopreserved; in other words, frozen at temperatures of -320.8 degrees Fahrenheit. While this system is very effective in the conservation of simple cells or tissues, in the case of larger organs the multiple cell types and other structures react in different ways to cold. To solve this problem, the team of Martin Yarmush and KorKut Uygun –researchers at Massachusetts General Hospital’s Centre for Medical Engineering in Boston-, have develop a preservation technique that has tripled the amount of time a rat liver can be stored before being transplanted.
The process, as described in “Nature Medicine”, consists in four steps. First, a machine perfusion is used; which is a technique to deliver oxygen and nutrients to the capillaries in the biological tissues, while remaining outside the body and being able of supercooling the hepatic tissue without irreversibly cell damaging. Second, to achieve this, the researchers added 3-OMG (3-O-methyl-D-glucose), a modified non-toxic glucose compound to the traditional solution. The 3-OMG, they explained, cannot be metabolized by liver cells, thus it accumulates in them; working as a cold shield. Third, the team also modified the solution by adding 35-kD (polyethylene glycol) to specifically protect cell membranes. Ethylene glycol is the active ingredient in anti-freeze, and it works by lowering the freezing point of a solution. Finally, the livers were then slowly cooled below the freezing point, to 21 degrees Fahrenheit, without inducing freezing, thereby supercooling the organ for preservation. After storing the organs for several days, the researchers again used machine perfusion to rewarm the organ, while also delivering oxygen and other nutrients to prepare the organ for transplantation.
Through this new technique, researchers were able to store supercooled rat livers during 3 days (72 hours) and 4 days (96 hours) at 21degrees Fahrenheit. All animals which received the livers stored for 3 days survived after three months and the survival rate of the rats receiving livers stored for four days were 58%; however, any of the animals that received livers with current method did.
To understand which steps of this system were essential, researchers tested eliminating the PEG-35 or 3-OMG, in both cases the animals died after a week; while the animals that receive livers that were not implemented the machine perfusion or the supercooling died after an hour of the transplant.
This technique must now go through extensive testing and be refined before they can think in use it in humans, but the first results are very encouraging. “The longer we are able to store the donated organs, the greater the likelihood that the patient can find the best possible organ” the researchers conclude.